Human malaria, caused by a protozoan sporozoa, is an acute and chronic protozoal disease caused by four species of plasmodia, namely Plasmodium falciparum, P. vivax, P. ovals and P. malarias. P. falciparum is the most virulent of these and the only one that kills acutely. The plasmodial parasites are transmitted by female mosquitoes of several species of the genus Anopheles. The World Health Organization recognizes malaria as the world's major primary health problem, causing more morbidity and mortality than any other disease. An estimated 300-500 million cases occur annually resulting in 3-5 million deaths, mostly among children. Malaria is a serious problem mainly in the tropical and subtropical world, especially Africa, South and Central America, India and Southeast Asia. Isolated cases of malaria have recently been reported in the southeastern and southwestern United States. The drug chloroquine is often used to treat malaria, however, the rapid spread of chloroquine-resistant P. falciparum and the lack of a malaria vaccine emphasizes the long-felt need to develop new strategies and agents for controlling this disease.
Babesiosis, an infection by protozoan sporozoa of the genus Babesia, is transmitted by hard-bodied ticks. The causative organisms, parasites resembling those of malaria, invade and destroy erythrocytes. Babesia infections in wild and domestic animals occur worldwide and are well known in veterinary medicine. Human infections are more rare and occur exclusively in Europe and North America. In many countries, Babesia is responsible for serious economic losses to the livestock industry. No effective chemotherapeutic treatment or vaccine has been known for treatment of babesiosis.
Taxol is a diterpenoid isolated from the stem bark of the western yew, Taxus brevifolia. Taxol is a mitotic spindle poison that stabilizes microtubules and inhibits their depolymerization to free tubulin. Taxol has been demonstrated to possess antineoplastic activity and has been identified as an anti-cancer agent, particularly in the treatment of advanced ovarian cancer.
Over ten years ago, Baum, et al. Proceeding of the National Academy of Science, U.S.A., 1981, 78, 4571-4575, found that taxol inhibited the flagellate protozoan Trypanosoa cruzi. Trypanosomes, being flagellated protozoans, belong to the protozoal Phylum mastigophora. Baum, et al. found that the addition of taxol inhibited the replication of T. cruzi in a dose-dependent fashion. Baum. et al. treated cultures containing trypanosomes with 1 nM to 10 .mu.M of taxol. However, treatment of trypanosomiasis was never developed and there are presently no efficacious and safe drugs for treating these infections, particularly the chronic forms.
Treatments for malaria and babesiosis have been similarly disappointing. Methods which are known for the treatment of malaria and babesiosis have not been satisfactory due to expense, limited efficacy, drug resistance, and safety. Methods for the treatment of malaria and babesiosis infections are greatly needed. The present invention provides methods satisfying this long-felt need.